Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many recent and significant advances in the field of chronic viral hepatitis, including therapy, suggest that an update on chronic hepatitis is timely. Chronic hepatitis B virus infection remains a significant worldwide cause of liver cirrhosis and hepatocellular carcinoma, despite the wide availability of a long established and effective vaccine. Transmission occurs via perinatal, sexual, and parenteral routes (particularly intravenous drug abuse and although blood products still carry a risk, this is now extremely low in Western countries). Only a minority of infected adult cases develop chronic hepatitis but in children under 1 year, 90% develop chronic hepatitis. The clinical spectrum of chronic liver injury ranges from mild inflammation to end stage liver cirrhosis. Interferon alfa has been the mainstay of treatment for patients with active disease but nucleoside analogues (lamivudine and adefovir) are now available with similar efficacy. Patients with end stage liver disease and hepatocellular carcinoma can be offered transplantation but infection in the graft is commonplace. The combination of hepatitis B immunoglobulin and newer antiviral drugs reduce the incidence and severity of graft infection significantly. The hepatitis C virus epidemic of the latter half of the 20th century now affects more than 1% of populations worldwide. This RNA virus is spread parenterally and is becoming the leading indication for liver transplantation. The majority of patients develop chronic hepatitis, which may be progressive, evolving to significant liver disease (cirrhosis or hepatocellular carcinoma) in about 20% cases after decades. Treatment with the combination of interferon alfa and ribavirin is successful in up to 40% cases. Liver transplantation is a therapeutic option for some but graft infection is universal and often complicated by progressive liver fibrosis. A vaccine remains a remote prospect so that prevention is crucial. Hepatitis D virus infection occurs on a background of hepatitis B virus infection and can also cause liver damage. The response to antiviral therapy is poor. The newer "hepatitis" viruses G and TT do not cause significant liver injury.
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PMID:Update on chronic viral hepatitis. 1147 Sep 28

Chronic hepatitis B virus (HBV) infection is known to be one of the major causes in the development of hepatocellular carcinoma (HCC), although the biomolecular mechanism(s) involved remain unclear. To identify the cellular gene(s) involved in HBV-associated hepatocarcinogenesis, we used the mRNA differential display method and examined three paired tumor and nontumor tissues, all of which had chromosomally integrated HBV-DNA through chronic infection. Using 240 different combinations of three one-base anchored oligo-dT primers and 80 arbitrary 13-mers, genes decreased or increased in expression more than twofold between each tumor tissue and its paired nontumor tissue were identified. Twenty-nine known genes and four novel genes were differentially over-expressed in the HCC tumor tissues. In contrast, 27 known genes and five novel genes were under-expressed in those tumor tissues. The nucleotide sequences of the nine novel gene fragments were determined and their expression patterns were examined in 40 HCC samples. HA61T2, PT18, HG63T1, and HG57T1 were preferentially over-expressed in 32 cases (80%, P<0.001), 24 cases (60%), 23 cases (57.5%) and 22 cases (55%) of the 40 tumor tissues, respectively. There was an increased frequency of HG57T1 over-expression in HCC patients with HBV-positive serology and low serum alpha-feto protein (AFP) levels (P<0.05). DNT10, PT8, PT19, ENT25 and HA6T4 were under-expressed in 26 cases (65%), 23 cases (57.5%), 21 cases (53%), 20 cases (50%) and 18 cases (45%) of the 40 tumor samples, respectively. There was a strong correlation of DNT10 under-expression with high serum AFP level in HCC patients, irrespective of HBV serology (P<0.01). HA6T4 was preferentially under-expressed in HCC tumors in patients with HBV-positive serology and high serum AFP levels (P<0.05). Thus, the functional analyses of the known and novel genes identified in this study should prove valuable to further understand the mechanism(s) of hepatocarcinogenesis.
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PMID:Expression profile of nine novel genes differentially expressed in hepatitis B virus-associated hepatocellular carcinomas. 1149 52

(1) Chronic hepatitis B is defined by the persistence of circulating HBs antigen for more than 6 months. Between 15 and 25% of chronic HBV carriers die prematurely of complications (mainly cirrhosis and hepatocellular carcinoma). (2) Patients with chronic hepatitis B rarely clear the virus spontaneously, but viral replication ceases in approximately 10% of patients annually, with disappearance of HBe and viral DNA, and emergence of anti-HBe antibodies. (3) Active viral replication and histologically proven liver necrosis are risk factors for progression to cirrhosis. (4) Antiviral treatments have been assessed only in patients with active viral replication. (5) Interferon alfa has been widely tested in the clinical setting. In one trial, in which patients were followed for 7 years, mortality was lower in the treatment group than in untreated controls. (6) Interferon alfa must be injected, and its administration may be followed by adverse effects such as a 'flu-like syndrome (frequently), psychiatric problems and potentially severe thyroid disorders. (7) Interferon alfa monotherapy for 4-6 months (possibly extended to 8-9 months) remains the first-line treatment for chronic hepatitis B. (8) Lamivudine has documented antiviral efficacy but its effect is only temporary in many patients. In the only trial comparing lamivudine with interferon alfa, lamivudine was no more effective than interferon in the short term (on the basis of serological and histological end points), despite a bias in its favour. Trials of lamivudine + interferon alfa in patients who fail to respond to interferon monotherapy have given unfavourable results. (9) Adverse effects are infrequent on lamivudine, but pharmacovigilance is required to assess potential hepatic and pancreatic effects at the dose used in this indication. (10) The long-term effects of lamivudine are unknown, especially on the risks of cirrhosis, hepatocarcinoma and the selection of resistant mutants. (11) Pending further data, lamivudine should be used only in clinical trials and cohort studies.
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PMID:Treatment of chronic hepatitis B: interferon alfa first. 1150 53

Chronic hepatitis B virus (HBV) infection and aflatoxin B(1) (AFB(1)) exposure interact synergetically to induce hepatocellular carcinoma. One suggested mechanism for this interaction is the enhanced activation of AFB(1) in chronically HBV-infected individuals. Whereas no associations between chronic HBV infection and AFB(1)-albumin adducts were observed in several studies in adults, hepatitis B surface antigen (HbsAg)-positive children were found to have elevated adducts in Gambia. To assess the association between chronic HBV infection and AFB(1)-albumin adduct level in Taiwan, 200 junior high school adolescents from 20 townships were assayed for HBsAg and AFB(1)-albumin adducts. The mean AFB(1)-albumin adduct level was higher in HBsAg-positive compared with HBsAg-negative subjects. The association between HBsAg status and AFB(1)-albumin adducts remained after multivariate adjustment. This finding additionally supports the synergetic interaction between HBV and AFB(1), but the mechanism remains to be elucidated.
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PMID:Association of aflatoxin B(1)-albumin adduct levels with hepatitis B surface antigen status among adolescents in Taiwan. 1170 Feb 73

Chronic hepatitis B infection is a global health problem that affects about 300 million people. Of these, 75% are Chinese. Most Chinese who become chronic carriers, contract the virus during the perinatal period. The natural history of these chronic hepatitis B carriers includes an initial immune tolerance phase, followed by immune clearance and an inactive hepatitis B non-replicative phase with the development of cirrhosis that may be complicated by hepatocellular carcinoma. The classification of hepato-cellular carcinoma has recently been revised. Based on immunohistochemical studies, it has been found that patients with hepatocellular carcinoma and biliary markers have a poorer survival than patients with hepatocellular carcinoma but who have negative biliary markers. Sometimes, a fourth phase, a hepatitis B envelope-negative hepatitis B virus replicative phase, reflecting the emergence of a pre-core mutant strain, may follow. Our improved understanding of the natural history of chronic hepatitis B infection has led to more effective approaches towards the control of this viral infection and its sequelae. Most importantly, immunisation against hepatitis B virus in the perinatal setting has been shown to prevent chronic infection.
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PMID:The natural history of chronic hepatitis B infection. 1184 73

Chronic hepatitis B virus (HBV) infection is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Its prevalence approaches 10% in hyper endemic areas. The aim of treating chronic HBV infection is to halt progression of liver injury by suppressing viral replication or eliminating infection. This study was planned to evaluate the advantages of combination therapy with interferon-alpha plus second-generation nucleoside analogues (lamivudine or famciclovir), or vaccination with a pre-S2 and S proteins containing vaccine in chronic HBV infection. 29 patients were divided into three groups and were treated with the following combinations: (1) IFN-alpha2a 9 million units 3x week for 6 months with HBV vaccine 20 microg given on 0, 1 and 2 months; (2) IFN-alpha2a 6 million units 3x week plus famciclovir 250 mg 3x day for 6 months; (3) IFN-alpha2a 6 million units 3x week plus lamivudine 100 mg/day for 6 months. Complete response was suspected in 3 patients in group 1, in 4 patients in group 2, and in 7 patients in group 3. Partial response was suspected in 4, 1 and 2 patients in groups 1, 2 and 3, respectively. The results of the present study suggest that the combination of IFN-alpha with lamivudine is more effective than the combination of IFN-alpha with HBV vaccination or famciclovir.
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PMID:Comparison of different treatment combinations for chronic hepatitis B infection. 1212 Aug 84

Chronic hepatitis B virus infection is common and may cause significant disease morbidity, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hepatitis B surface antigen-positive patients should have a detailed serologic evaluation including determination of the level of replication. Patients with high levels of virus replication and those with co-infection should be considered for treatment. Interferon was the first approved therapy for chronic hepatitis B and remains one of the most effective options. Newer agents, such as lamivudine and adefovir dipivoxil, offer excellent antiviral activity and ease of administration, although drug resistance is common with lamivudine.
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PMID:Update on the management of chronic hepatitis B. 1222 14

Chronic hepatitis B virus (HBV) infection can cause a broad spectrum diseases, including from asymptomatic HBV carriers or cryptic hepatitis, to acute hepatitis, chronic hepatitis, Liver cirrhosis and primary hepatocellular carcinoma. The variable pattern and clinical outcome of the infection were mainly determined by virological itself factors, host immunological factors and genetic factors as well as the experimental factors. Among the human genetic factors, major candidate or identified genes involved in the process of HBV infection fall into the following categories: (1) genes that mediate the processes of viral entry into hepatocytes, including genes involved in viral binding, fusion with cellular membrane and transportation in target cells; (2) genes that modulate or control the immune response to HBV infection; (3) genes that participate in the pathological alterations in liver tissue; (4) genes involved in the development of liver cirrhosis and hepatocellular carcinoma associated with chronic HBV infection, including genes related to mother-to-infant transmission of HBV infection; and (5) those that contribute to resistance to antiviral therapies. Most of the reports of human genes associated with HBV infection have currently focused on HLA associations. For example, some investigators reported the association of the HLA class II alleles such as DRB1*1302 or HLA-DR13 or DQA1*0501-DQB1*0301-DQB1*1102 haplotypes with acute and/or chronic hepatitis B virus infection, respectively. Several pro-inflammatory cytokines such as Th1 cytokines (including IL-2 and IFN-gamma) and TNF-alpha have been identified to participate the process of viral clearance and host immune response to HBV. In contrast, the Th2 cytokine IL-10 serves as a potent inhibitor of Th1 effector cells in HBV diseases. The MBP polymorphisms in its encoding region were found to be involved in chronic infection. Thus, reports from various laboratories have shown some inconsistencies with regard to the effects of host genetic factors on HBV clearance and persistence. Since genetic interactions are complex, it is unlikely that a single allelic variant is responsible for HBV resistance or susceptibility. However, the collective influence of several single nucleotide polymorphisms (SNPs) or haplotype (s) may underlie the natural combinational or synergistic protection against HBV. The future study including the multi-cohort collaboration will be needed to clarify these preliminary associations and identify other potential candidate genes. The ongoing study of the distributions and functions of the implicated allele polymorphisms will not only provide insight into the pathogenesis of HBV infection, but may also provide a novel rationale for new methods of diagnosis and therapeutic strategies.
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PMID:Current status and prospects of studies on human genetic alleles associated with hepatitis B virus infection. 1267 1

Chronic hepatitis B remains a public health problem of global importance despite the availability of an effective vaccine. Between 350 and 400 million people, approximately 6% of the world's population, suffer from chronic hepatitis B and face a 30% likelihood of developing cirrhotic liver disease or hepatocellular carcinoma. Current treatment options include three monotherapies of subcutaneous interferon, oral nucleoside lamivudine and oral nucleotide adefovir dipivoxil. Unfortunately, these agents have not effectively and frequently been able to attain a 'cure' or complete eradication of the virus. Consequently, the expectation of current therapies is confined to the achievement of clinically beneficial and durable responses defined by lasting suppression of virus replication, histological improvement and increased survival for patients with decompensated liver diseases. Other disadvantages include the undesirable tolerability of interferon, the rapid resistance to lamivudine and the compromise between efficacy and toxicity that led to the development of the 10 mg dose of adefovir dipivoxil. Clearly, better therapeutics and treatment strategies are needed. Increased potency, activity against current treatment-refractory viruses, as well as efficacy in difficult-to-treat populations will be critical to meeting the therapeutic challenge of chronic hepatitis B.
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PMID:Agents in clinical development for the treatment of chronic hepatitis B. 1288 17

Chronic hepatitis B virus (HBV) infection, which can lead to cirrhosis and hepatocellular carcinoma, is a major health threat worldwide. Classic patients with chronic hepatitis B are positive for hepatitis Be-antigen (HBeAg) and HBV-DNA. In the Mediterranean basin, 30-80% of patients with chronic hepatitis B (CHB) are HBeAg-negative, in contrast to Northern European countries and the US, where only 10-40% of CHB patients are lacking HbeAg. HBeAg-negative CHB usually runs a progressive course. The greatest problem with the treatment of HBeAg-negative CHB is the high relapse rate. Their end treatment response rates are similar to those of classic CHB patients, but after discontinuation of treatment most of them relapse. All the data available in the literature show that more than 80% of patients with HBeAg-negative CHB do not respond to the current approved therapies. A literature review and our experience with thymosin indicate that the combination of IFN alpha2b and T-alpha1 is better tolerated and more likely to induce a sustained response in HbeAg-negative chronic hepatitis B patients when compared to other currently available therapies. As thymosin-alpha1 treatment is relatively free from adverse effects, future controlled trials are needed, with a longer follow-up, in order to fully evaluate the role of the combination therapy of thymosin-alpha1 with other emerging therapeutic agents.
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PMID:Thymosin in the treatment of HBeAg-negative chronic hepatitis B. 1294 46


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